The studies that are planned are directed toward the understanding of the mechanism of persistent viral infection in cell culture model systems using vesicular stomatitis, influenza type A, and Newcastle disease viruses. Special emphasis will be placed on analysis of the evolution of virus and host cells during long-term persistent infections. The information obtained may have pertinence to human illnesses which involve persistent viral infections. The importance of such diseases is being increasingly recognized. Investigations will be continued dealing with the mechanism of action of interferon. Particular emphasis will be placed on characterization of an effect of interferon recently discovered in this laboratory, namely, inhibition of cellular endocytosis and virus uptake. This effect of interferon is potentially relevant to the use of interferon as an antiviral and antitumor agent. In addition, the first example of a virus activity which can overcome an interferon-induced function (i.e., double-stranded RNA-dependent protein kinase) will be investigated and characterized. Besides evaluating the role of the interferon-induced protein kinase in interferon-mediated restriction of viral protein synthesis, these studies may provide insight into the mechanism of eukaryotic protein synthesis and its alteration by virus infection. The mechanism of virus-mediated inhibition of endocytosis and superinfection exclusion will be further investigated. These studies will yield valuable information concerning the influence of viral infection on host cell plasma membrane function and on the mechanism of entry of virus into cells.